Obesity has been cited as the most prevalent nutrition problem in America. In the light of overwhelming evidence obesity has been described as a "disease" that is associated with significant morbidity and mortality. Unfortunately the treatments of obesity have been largely unsuccessful. With the past 20 ys there has been a plethora of popular diets that promote rapid weight loss. Semistarvation (SS) or very low calorie, high protein were designed to overcome the adverse effects of negative N balance and subsequent loss of lean muscle mass that occurs with total fasting. The safety and efficacy of these diets were strongly challenged following reports of adverse effects and of deaths associated with this approach to weight reduction. Appropriately supplemented SS diets have been reported to be more successful nevertheless, these diets are considered to constitute a potentially lethal complication of rapid massive weight loss, particularly when used without appropriate medical supervision. This proposal is designed to study SS and subsequent refeeding (RF) in a systemic, controlled animal model, the rat. This model is selected so that the adaptive response to SS and RF can be determined in specific organ systems of the gastrointestinal tract and heart. These two organ systems are selected because: 1) specific pathogenesis of cardiac complications associated with rapid, massive weight loss have not yet been satisfactorily explained, and the rapid reversal of semistarvation by RF may trigger cardiac aberrations that are not fully understood; 2) the effects of SS and RF and the gut have been almost completely ignored even though this organ system creates the interface between dietary nutrients and subsequent metabolism and utilization. This study will utilize a nutritionally complete defined formula diet (control = C), or a nutritionally complete but low calorie defined formula diet (semistarvation = SS). Dietary obese rats will be randomly placed in C, SS to RF (semistarvation to refeeding) groups. Varying durations of SS and RF will allow assessment of acute as well as chronic effects of both SS and RF. Nitrogen (N) economy will be determined serially by N balance (urinary and fecal N). Bioelectrical impedance analysis will be utilized to serially measure body composition of experimental animals, including % fat, lean body mass, total body water. Following terminal bioelectrical impedance, direct analysis of carcasses will be performed allowing a comparison of bioelectrical impedance vs chemical analysis of body composition of the experimental animals. Nitrogen economy will also be assessed by determination of protein, RNA, DNA concentration of cardiac and g.i. organ (pancreas, liver, small intestine) tissues. Comparative studies will be made of selected pancreatic enzyme activity (amylase, chymotrypsin, trypsin); intestinal enzymes (maltase, sucrase, lactase); liver lipid concentration; cardiac Ca, K, P, Zn, Cu and Mg concentrations. Histology will assess the morphological characteristics of the hepatic, pancreatic, intestinal and cardiac tissue, and detailed analysis of cardiac ultrastructure by electron microscopy will be performed. Cardiac function will be serially monitored by in vivo direct recording of electrocardiograms subjected to computer analysis. The 14C-aminopyrine breath test will be performed to assess dynamic liver functional capacity. Intestinal absorptive function of the duodenum and ileum will be assessed using a jejunal gut sac transport system. Because of the escalating but controversial therapy employing SS and RF diets, and because of the potential seriousness as well as successful of this treatment, the development of an animal model to study selected organ systems is a high priority that will provide knowledge and understanding applicable to clinical treatment of obesity and maintenance of weight loss during RF.